The Clinical Epilepsy Section continues to study the clinical pharmacology of old and new antiepileptic drugs. Special emphasis has been placed on studies of new antiepileptic compounds, such as flupirtine. Flupirtine is being evaluated both clinically and pharmacologically in patients with either complex partial or absence seizures. Flupirtine is especially promising in models of epilepsy and preliminary clinical results are encouraging. A new protocol for the use of progabide, as well as gamma vinyl GABA, in children with the Lennox-Gastaut syndrome has been approved by the NINCDS-ICRS, but studies of both these compounds are awaiting FDA approval. These drugs, although chemically unrelated, are thought to act by increasing CNS levels of gamma amino butyric acid (GABA), a putative inhibitory neurotransmitter. Measurements of changes in CSF GABA levels due to the drugs will be correlated with their effects on seizure control. Studies have been undertaken on the unusual pharmacokinetics of phenytoin, establishing a "pseudo steady-state" phenomenon based on clinical observation made possible by the intensive monitoring unit of the Clinical Epilepsy Section. This phenomenon helps explain some of the difficulties physicians have when they use this drug, and provides a theoretical framework for future investigations of this difficult pharmacologic problem. The pharmacologic evaluation of antiepileptic drugs is coupled with efficacy studies, carried out by intensive monitoring techniques including videotape analysis of epileptic seizures with simultaneous telemetered EEG recording, and daily determination of antiepileptic drug levels. Future studies are planned to evaluate the specific patterns of hepatic microsomal enzyme metabolism of antiepileptic drugs by evaluating antipyrine metabolites.